20 results on '"Vallentgoed, Wies R"'
Search Results
2. Alternative normalization and analysis pipeline to address systematic bias in NanoString GeoMx Digital Spatial Profiling data
- Author
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van Hijfte, Levi, Geurts, Marjolein, Vallentgoed, Wies R., Eilers, Paul H.C., Sillevis Smitt, Peter A.E., Debets, Reno, and French, Pim J.
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- 2023
- Full Text
- View/download PDF
3. Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4: A systematic review
- Author
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Tesileanu, C. Mircea S., Vallentgoed, Wies R., French, Pim J., and van den Bent, Martin J.
- Published
- 2022
- Full Text
- View/download PDF
4. The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen
- Author
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Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, et al, Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, and et al
- Abstract
Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histological progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution towards an IDHwt-like phenotype.
- Published
- 2024
5. Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations
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Tesileanu, C. Mircea S., Vallentgoed, Wies R., Sanson, Marc, Taal, Walter, Clement, Paul M., Wick, Wolfgang, Brandes, Alba Ariela, Baurain, Jean Francais, Chinot, Olivier L., Wheeler, Helen, Gill, Sanjeev, Griffin, Matthew, Rogers, Leland, Rudà, Roberta, Weller, Michael, McBain, Catherine, Reijneveld, Jaap, Enting, Roelien H., Caparrotti, Francesca, Lesimple, Thierry, Clenton, Susan, Gijtenbeek, Anja, Lim, Elizabeth, de Vos, Filip, Mulholland, Paul J., Taphoorn, Martin J. B., de Heer, Iris, Hoogstrate, Youri, de Wit, Maurice, Boggiani, Lorenzo, Venneker, Sanne, Oosting, Jan, Bovée, Judith V. M. G., Erridge, Sara, Vogelbaum, Michael A., Nowak, Anna K., Mason, Warren P., Kros, Johan M., Wesseling, Pieter, Aldape, Ken, Jenkins, Robert B., Dubbink, Hendrikus J., Baumert, Brigitta, Golfinopoulos, Vassilis, Gorlia, Thierry, van den Bent, Martin, and French, Pim J.
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- 2021
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6. Epigenetic landscape reorganization and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma
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Ghisai, Santoesha A, primary, van Hijfte, Levi, additional, Vallentgoed, Wies R, additional, Tesileanu, C Mircea S, additional, de Heer, Iris, additional, Kros, Johan M, additional, Sanson, Marc, additional, Gorlia, Thierry, additional, Wick, Wolfgang, additional, Vogelbaum, Michael A, additional, Brandes, Alba A, additional, Franceschi, Enrico, additional, Clement, Paul M, additional, Nowak, Anna K, additional, Golfinopoulos, Vassilis, additional, van den Bent, Martin J, additional, French, Pim J, additional, and Hoogstrate, Youri, additional
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- 2024
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7. Evolutionary trajectories of IDH-mutant astrocytoma identify molecular grading markers related to cell cycling
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Vallentgoed, Wies R., primary, Hoogstrate, Youri, additional, van Garderen, Karin A., additional, van Hijfte, Levi, additional, van Dijk, Erik, additional, Kouwenhoven, Mathilde C. M., additional, Niers, Johanna M., additional, Draaisma, Kaspar, additional, Martin, Ivonne, additional, de Leng, Wendy W. J., additional, Tesileanu, C. Mircea S., additional, de Heer, Iris, additional, Diepeveen, Maud, additional, Lavrova, Anna, additional, Eijk, Paul P., additional, Bühler, Marcel, additional, Wick, Wolfgang, additional, Clement, Paul M., additional, Sanson, Marc, additional, Franceschi, Enrico, additional, Gorlia, Thierry, additional, Golfinopoulos, Vassilis, additional, Weller, Michael, additional, Weiss, Tobias, additional, Robe, Pierre A., additional, Kros, Johan M., additional, Smits, Marion, additional, van de Wiel, Mark, additional, Ylstra, Bauke, additional, Verhaak, Roel G. W., additional, van den Bent, Martin J., additional, Westerman, Bart A., additional, Wesseling, Pieter, additional, and French, Pim J., additional
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- 2024
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8. The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen
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Malta, Tathiane M., primary, Sabedot, Thais S., additional, Morosini, Natalia S., additional, Datta, Indrani, additional, Garofano, Luciano, additional, Vallentgoed, Wies R., additional, Varn, Frederick S., additional, Aldape, Kenneth, additional, D'Angelo, Fulvio, additional, Bakas, Spyridon, additional, Barnholtz-Sloan, Jill S., additional, Gan, Hui K., additional, Hasanain, Mohammad, additional, Hau, Ann-Christin, additional, Johnson, Kevin C., additional, Cazacu, Simona, additional, deCarvalho, Ana C., additional, Khasraw, Mustafa, additional, Kocakavuk, Emre, additional, Kouwenhoven, Mathilde C.M., additional, Migliozzi, Simona, additional, Niclou, Simone P., additional, Niers, Johanna M., additional, Ormond, D. Ryan., additional, Paek, Sun Ha, additional, Reifenberger, Guido, additional, Sillevis Smitt, Peter A., additional, Smits, Marion, additional, Stead, Lucy F., additional, van den Bent, Martin J., additional, Van Meir, Erwin G., additional, Walenkamp, Annemiek, additional, Weiss, Tobias, additional, Weller, Michael, additional, Westerman, Bart A., additional, Ylstra, Bauke, additional, Wesseling, Pieter, additional, Lasorella, Anna, additional, French, Pim J., additional, Poisson, Laila M., additional, Consortium, The GLASS, additional, Verhaak, Roel G.W., additional, Iavarone, Antonio, additional, and Noushmehr, Houtan, additional
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- 2023
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9. Longitudinal characteristics of T2-FLAIR mismatch in IDH-mutant astrocytomas: relation to grade, histopathology and overall survival in the GLASS-NL cohort
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van Garderen, Karin A, primary, Vallentgoed, Wies R, additional, Lavrova, Anna, additional, Niers, Johanna M, additional, de Leng, Wendy W J, additional, Hoogstrate, Youri, additional, de Heer, Iris, additional, Ylstra, Bauke, additional, van Dijk, Erik, additional, Klein, Stefan, additional, Draaisma, Kaspar, additional, Robe, Pierre A J T, additional, Verhaak, Roel G W, additional, Westerman, Bart A, additional, French, Pim J, additional, van den Bent, Martin J, additional, Kouwenhoven, Mathilde C M, additional, Kros, Johan M, additional, Wesseling, Pieter, additional, and Smits, Marion, additional
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- 2023
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10. Longitudinal characteristics of T2-FLAIR mismatch in IDH-mutant astrocytomas:Relation to grade, histopathology, and overall survival in the GLASS-NL cohort
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Van Garderen, Karin A., Vallentgoed, Wies R., Lavrova, Anna, Niers, Johanna M., De Leng, Wendy W.J., Hoogstrate, Youri, De Heer, Iris, Ylstra, Bauke, Van Dijk, Erik, Klein, Stefan, Draaisma, Kaspar, Robe, Pierre A.J.T., Verhaak, Roel G.W., Westerman, Bart A., French, Pim J., Van Den Bent, Martin J., Kouwenhoven, Mathilde C.M., Kros, Johan M., Wesseling, Pieter, Smits, Marion, Van Garderen, Karin A., Vallentgoed, Wies R., Lavrova, Anna, Niers, Johanna M., De Leng, Wendy W.J., Hoogstrate, Youri, De Heer, Iris, Ylstra, Bauke, Van Dijk, Erik, Klein, Stefan, Draaisma, Kaspar, Robe, Pierre A.J.T., Verhaak, Roel G.W., Westerman, Bart A., French, Pim J., Van Den Bent, Martin J., Kouwenhoven, Mathilde C.M., Kros, Johan M., Wesseling, Pieter, and Smits, Marion
- Abstract
Background: The T2-FLAIR mismatch sign is defined by signal loss of the T2-weighted hyperintense area with Fluid-Attenuated Inversion Recovery (FLAIR) on magnetic resonance imaging, causing a hypointense region on FLAIR. It is a highly specific diagnostic marker for IDH-mutant astrocytoma and is postulated to be caused by intercellular microcystic change in the tumor tissue. However, not all IDH-mutant astrocytomas show this mismatch sign and some show the phenomenon in only part of the lesion. The aim of the study is to determine whether the T2-FLAIR mismatch phenomenon has any prognostic value beyond initial noninvasive molecular diagnosis. Methods: Patients initially diagnosed with histologically lower-grade (2 or 3) IDH-mutant astrocytoma and with at least 2 surgical resections were included in the GLASS-NL cohort. T2-FLAIR mismatch was determined, and the growth pattern of the recurrent tumor immediately before the second resection was annotated as invasive or expansive. The relation between the T2-FLAIR mismatch sign and tumor grade, microcystic change, overall survival (OS), and other clinical parameters was investigated both at first and second resection. Results: The T2-FLAIR mismatch sign was significantly related to Grade 2 (80% vs 51%), longer post-resection median OS (8.3 vs 5.2 years), expansive growth, and lower age at second resection. At first resection, no relation was found between the mismatch sign and OS. Microcystic change was associated with areas of T2-FLAIR mismatch. Conclusions: T2-FLAIR mismatch in IDH-mutant astrocytomas is correlated with microcystic change in the tumor tissue, favorable prognosis, and Grade 2 tumors at the time of second resection.
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- 2023
11. Longitudinal characteristics of T2-FLAIR mismatch in IDH-mutant astrocytomas: Relation to grade, histopathology, and overall survival in the GLASS-NL cohort
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Pathologie Pathologen staf, Cancer, Opleiding Neurochirurgie, Brain, van Garderen, Karin A, Vallentgoed, Wies R, Lavrova, Anna, Niers, Johanna M, de Leng, Wendy W J, Hoogstrate, Youri, de Heer, Iris, Ylstra, Bauke, van Dijk, Erik, Klein, Stefan, Draaisma, Kaspar, Robe, Pierre A J T, Verhaak, Roel G W, Westerman, Bart A, French, Pim J, van den Bent, Martin J, Kouwenhoven, Mathilde C M, Kros, Johan M, Wesseling, Pieter, Smits, Marion, Pathologie Pathologen staf, Cancer, Opleiding Neurochirurgie, Brain, van Garderen, Karin A, Vallentgoed, Wies R, Lavrova, Anna, Niers, Johanna M, de Leng, Wendy W J, Hoogstrate, Youri, de Heer, Iris, Ylstra, Bauke, van Dijk, Erik, Klein, Stefan, Draaisma, Kaspar, Robe, Pierre A J T, Verhaak, Roel G W, Westerman, Bart A, French, Pim J, van den Bent, Martin J, Kouwenhoven, Mathilde C M, Kros, Johan M, Wesseling, Pieter, and Smits, Marion
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- 2023
12. Molecular markers related to patient outcome in patients with IDH-mutant astrocytomas grade 2 to 4:A systematic review
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Tesileanu, C. Mircea S., Vallentgoed, Wies R., French, Pim J., van den Bent, Martin J., Tesileanu, C. Mircea S., Vallentgoed, Wies R., French, Pim J., and van den Bent, Martin J.
- Abstract
Background: Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4. Methods: A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53. Results: The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies. Conclusions: Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
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- 2022
13. Abstract 1228: Spatial transcriptomics: Data processing revisited to address noise interference
- Author
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van Hijfte, Levi, primary, Geurts, Marjolein, additional, Vallentgoed, Wies R., additional, Eilers, Paul H., additional, Smitt, Peter A. Sillevis, additional, Debets, Reno, additional, and French, Pim J., additional
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- 2022
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14. Longitudinal characteristics of T2-FLAIR mismatch in IDH-mutant astrocytomas: Relation to grade, histopathology, and overall survival in the GLASS-NL cohort.
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Garderen, Karin A van, Vallentgoed, Wies R, Lavrova, Anna, Niers, Johanna M, Leng, Wendy W J de, Hoogstrate, Youri, Heer, Iris de, Ylstra, Bauke, Dijk, Erik van, Klein, Stefan, Draaisma, Kaspar, Robe, Pierre A J T, Verhaak, Roel G W, Westerman, Bart A, French, Pim J, Bent, Martin J van den, Kouwenhoven, Mathilde C M, Kros, Johan M, Wesseling, Pieter, and Smits, Marion
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- 2023
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15. Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations.
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UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Tesileanu, C Mircea S, Vallentgoed, Wies R, Sanson, Marc, Taal, Walter, Clement, Paul M, Wick, Wolfgang, Brandes, Alba Ariela, Baurain, Jean-François, Chinot, Olivier L, Wheeler, Helen, Gill, Sanjeev, Griffin, Matthew, Rogers, Leland, Rudà, Roberta, Weller, Michael, McBain, Catherine, Reijneveld, Jaap, Enting, Roelien H, Caparrotti, Francesca, Lesimple, Thierry, Clenton, Susan, Gijtenbeek, Anja, Lim, Elizabeth, de Vos, Filip, Mulholland, Paul J, Taphoorn, Martin J B, de Heer, Iris, Hoogstrate, Youri, de Wit, Maurice, Boggiani, Lorenzo, Venneker, Sanne, Oosting, Jan, Bovée, Judith V M G, Erridge, Sara, Vogelbaum, Michael A, Nowak, Anna K, Mason, Warren P, Kros, Johan M, Wesseling, Pieter, Aldape, Ken, Jenkins, Robert B, Dubbink, Hendrikus J, Baumert, Brigitta, Golfinopoulos, Vassilis, Gorlia, Thierry, van den Bent, Martin, French, Pim J, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, Tesileanu, C Mircea S, Vallentgoed, Wies R, Sanson, Marc, Taal, Walter, Clement, Paul M, Wick, Wolfgang, Brandes, Alba Ariela, Baurain, Jean-François, Chinot, Olivier L, Wheeler, Helen, Gill, Sanjeev, Griffin, Matthew, Rogers, Leland, Rudà, Roberta, Weller, Michael, McBain, Catherine, Reijneveld, Jaap, Enting, Roelien H, Caparrotti, Francesca, Lesimple, Thierry, Clenton, Susan, Gijtenbeek, Anja, Lim, Elizabeth, de Vos, Filip, Mulholland, Paul J, Taphoorn, Martin J B, de Heer, Iris, Hoogstrate, Youri, de Wit, Maurice, Boggiani, Lorenzo, Venneker, Sanne, Oosting, Jan, Bovée, Judith V M G, Erridge, Sara, Vogelbaum, Michael A, Nowak, Anna K, Mason, Warren P, Kros, Johan M, Wesseling, Pieter, Aldape, Ken, Jenkins, Robert B, Dubbink, Hendrikus J, Baumert, Brigitta, Golfinopoulos, Vassilis, Gorlia, Thierry, van den Bent, Martin, and French, Pim J
- Abstract
Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1 mutations. Patients harbouring IDH1 mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1 have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1 mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.
- Published
- 2021
16. Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations
- Author
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Tesileanu, C Mircea S, Vallentgoed, Wies R, Sanson, Marc, Taal, Walter, Clement, Paul M, et al, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Tesileanu, C Mircea S, Vallentgoed, Wies R, Sanson, Marc, Taal, Walter, Clement, Paul M, et al, and Weller, Michael; https://orcid.org/0000-0002-1748-174X
- Abstract
Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1R132H mutations. Patients harbouring IDH1R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1R132H have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1R132H mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication. Keywords: Astrocytoma; Gene expression; Genome-wide DNA methylation; IDH1; IDH2.
- Published
- 2021
17. DNA methylation and survival differences associated with the type of IDH mutation in 1p/19q non-codeleted astrocytomas
- Author
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Tesileanu, C Mircea S, primary, Vallentgoed, Wies R, additional, Sanson, Marc, additional, Taal, Walter, additional, Clement, Paul M, additional, Wick, Wolfgang, additional, Brandes, Alba Ariela, additional, Baurain, Jean Francais, additional, Chinot, Olivier L, additional, Wheeler, Helen, additional, Gill, Sanjeev, additional, Griffin, Matthew, additional, Rogers, Leland, additional, Rudà, Roberta, additional, Weller, Michael, additional, McBain, Catherine, additional, Reijneveld, Jaap, additional, Enting, Roelien H, additional, Caparrotti, Francesca, additional, Lesimple, Thierry, additional, Clenton, Susan, additional, Gijtenbeek, Anja, additional, Lim, Elisabeth, additional, de Vos, Filip, additional, Mulholland, Paul J, additional, Taphoorn, Martin J B, additional, de Heer, Iris, additional, Hoogstrate, Youri, additional, de Wit, Maurice, additional, Boggiani, Lorenzo, additional, Venneker, Sanne, additional, Oosting, Jan, additional, Bovée, Judith VMG, additional, Erridge, Sara, additional, Vogelbaum, Michael A, additional, Nowak, Anna K, additional, Mason, Warren P, additional, Kros, Johan M, additional, Wesseling, Pieter, additional, Aldape, Ken, additional, Jenkins, Robert B, additional, Dubbink, Hendrikus J, additional, Baumert, Brigitta, additional, Golfinopoulos, Vassilis, additional, Gorlia, Thierry, additional, van den Bent, Martin, additional, and French, Pim J, additional
- Published
- 2020
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18. Finding the Right Way to Target EGFR in Glioblastomas; Lessons from Lung Adenocarcinomas.
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Gao, Ya, Vallentgoed, Wies R., and French, Pim J.
- Subjects
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ADENOCARCINOMA , *EPIDERMAL growth factor , *GENE amplification , *GLIOMAS , *LUNG tumors , *GENETIC mutation , *PROTEIN-tyrosine kinase inhibitors - Abstract
The EGFR gene is one of the most frequently mutated and/or amplified gene both in lung adenocarcinomas (LUAD) and in glioblastomas (GBMs). Although both tumor types depend on the mutation for growth, clinical benefit of EGFR tyrosine kinase inhibitors (TKIs) has only been observed in LUAD patients and, thus-far, not in GBM patients. Also in LUAD patients however, responses are restricted to specific EGFR mutations only and these 'TKI-sensitive' mutations hardly occur in GBMs. This argues for mutation-specific (as opposed to tumor-type specific) responses to EGFR-TKIs. We here discuss potential reasons for the differences in mutation spectrum and highlight recent evidence for specific functions of different EGFR mutations. These mutation-specific effects likely underlie the differential treatment response between LUAD and GBMs and provide new insights into how to target EGFR in GBM patients. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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19. Epigenetic landscape reorganization and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma.
- Author
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Ghisai SA, van Hijfte L, Vallentgoed WR, Tesileanu CMS, de Heer I, Kros JM, Sanson M, Gorlia T, Wick W, Vogelbaum MA, Brandes AA, Franceschi E, Clement PM, Nowak AK, Golfinopoulos V, van den Bent MJ, French PJ, and Hoogstrate Y
- Abstract
Accurate grading of IDH-mutant gliomas defines patient prognosis and guides the treatment path. Histological grading is however difficult and, apart from CDKN2A/B homozygous deletions in IDH-mutant astrocytomas, there are no other objective molecular markers used for grading. Experimental Design: RNA-sequencing was conducted on primary IDH-mutant astrocytomas (n=138) included in the prospective CATNON trial, which was performed to assess the prognostic effect of adjuvant and concurrent temozolomide. We integrated the RNA sequencing data with matched DNA-methylation and NGS data. We also used multi-omics data from IDH-mutant astrocytomas included in the TCGA dataset and validated results on matched primary and recurrent samples from the GLASS-NL study. We used the DNA-methylation profiles to generate a Continuous Grading Coefficient (CGC) that is based on classification scores derived from a CNS-tumor classifier. We found that the CGC was an independent predictor of survival outperforming current WHO-CNS5 and methylation-based classification. Our RNA-sequencing analysis revealed four distinct transcription clusters that were associated with i) an upregulation of cell cycling genes; ii) a downregulation of glial differentiation genes; iii) an upregulation of embryonic development genes (e.g. HOX, PAX and TBX) and iv) an upregulation of extracellular matrix genes. The upregulation of embryonic development genes was associated with a specific increase of CpG island methylation near these genes.
- Published
- 2024
- Full Text
- View/download PDF
20. Alternative normalization and analysis pipeline to address systematic bias in NanoString GeoMx Digital Spatial Profiling data.
- Author
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van Hijfte L, Geurts M, Vallentgoed WR, Eilers PHC, Sillevis Smitt PAE, Debets R, and French PJ
- Abstract
Spatial transcriptomics is a novel technique that provides RNA-expression data with tissue-contextual annotations. Quality assessments of such techniques using end-user generated data are often lacking. Here, we evaluated data from the NanoString GeoMx Digital Spatial Profiling (DSP) platform and standard processing pipelines. We queried 72 ROIs from 12 glioma samples, performed replicate experiments of eight samples for validation, and evaluated five external datasets. The data consistently showed vastly different signal intensities between samples and experimental conditions that resulted in biased analysis. We evaluated the performance of alternative normalization strategies and show that quantile normalization can adequately address the technical issues related to the differences in data distributions. Compared to bulk RNA sequencing, NanoString DSP data show a limited dynamic range which underestimates differences between conditions. Weighted gene co-expression network analysis allowed extraction of gene signatures associated with tissue phenotypes from ROI annotations. Nanostring GeoMx DSP data therefore require alternative normalization methods and analysis pipelines., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
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